Time-dependent effects of striatal interleukin-2 on open field behaviour in rats

Time-dependent effects of striatal interleukin-2 on open field behaviour in rats
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DOI:
10.1016/j.jneuroim.2008.12.003
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发表时间:
2009-03-31
影响因子:
3.3
通讯作者:
Pawlak, Cornelius R.
Pawlak, Cornelius R.
中科院分区:
医学4区
文献类型:
--
作者:
Karrenbauer, Britta D.;Ho, Ying-Jui;Pawlak, Cornelius R.

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有证据表明,像细胞因子这样的免疫信使可以调节情绪和动机行为,并与焦虑、抑郁等精神疾病有关。在此之前,我们已经证明了细胞因子基因(白介素2)在特定脑组织(纹状体、前额叶皮质)的表达与焦虑样行为(张开手臂时间)有关。在随后的实验中,单次纹状体注射IL-2显示出行为趋势,较低剂量(1毫微克)表现为行为抑制方式,而最高剂量(25毫微克)则导致激活和类焦虑行为。在这里,为了支持和扩展我们之前的发现,我们测试了Wistar杂交大鼠,在单侧(脑平衡部位)注射IL-2到腹侧/背侧纹状体后,急性和24小时后进行开场测试。对水平运动的分析显示,两组之间没有差异。然而,与1 ng组和24小时后的赋形剂对照组相比,接受IL-2处理(0.1 ng)的大鼠表现出剂量依赖性的回避效应(即中心时间缩短)。此外,在急性试验和部分24小时后,与生理盐水相比,两种剂量的IL-2(0.1;1 ng)都显示出抑制自由放养活动的作用。因此,在实验2中,我们测试了主动药物机制,以测试在实验1中观察到的IL-2的延迟效应。在一个新的样本中,大鼠在纹状体注射IL-2(0.1:0.01;0 ng)后回到家中,并在注射后24小时和48小时在开放的野外进行测试。无论是第一次(24小时)还是第二次(48小时后),分析都没有显示出任何显著的行为影响。因此,我们认为纹状体IL-2可以调节情绪相关行为至少24小时。然而,只有在注射后立即进行轻度应激环境挑战(即强迫露天暴露)时,才能观察到这种IL-2效应。总而言之,纹状体IL-2对旷场行为的影响可以排除主动药物的影响。(C)2008爱思唯尔B.V.保留所有权利。
There is evidence that immune messengers like cytokines can modulate emotional and motivated behaviours and are involved in psychiatric conditions like anxiety, and depression. Previously, we showed that cytokine geneexpression (interleukin (IL)-2 mRNA)in specific brain tissues (striatum, prefrontal cortex) correlated with anxiety-like behaviour (open arm time) in an elevated plus-maze in rats. In a subsequent experiment, a single striatal IL-2 injection showed behavioural trends with the lower dose (1 ng) acting in a behavioural suppressive way, whereas the highest dosage (25 ng) led to activation and anxiolytic-like behaviour. Here, to support and extend our previous findings, we tested Wistar outbred rats after a single unilateral (balanced brain sites) IL-2 injection into the ventral/dorsal striatum followed by an open field test acutely and 24 h later. Analyses for horizontal locomotion showed no differences between groups. However, rats with IL-2-treatment (0.1 ng) showed a dose-dependent avoidance effect (i.e. reduced centre time) compared to the 1 ng group and vehicle controls 24 h later. In addition, suppression of free rearing activity was shown for both IL-2 doses (0.1; 1 ng) compared to saline in the acute test, and partly 24 h later. Thus, in experiment 2, we tested for proactive drug mechanisms to test for delayed effects of IL-2 as observed in experiment 1. In a new sample, rats were returned to their home cages after a striatal IL-2 injection (0.1: 0.01; 0 ng), and tested 24 h and 48 h after the injection in an open field. Neither for the first (24 h) nor for the second exposure (48 h later) did the analyses show any significant behavioural effects. We therefore suggest that emotional-related behaviour can be modulated by striatal IL-2 for at least 24 h. However, such IL-2 effects can only be observed if a mild stressful environmental challenge (i.e., forced open field exposure) is followed immediately after injection. In conclusion, proactive drug effects may be excluded for striatal IL-2 effects on open field behaviour. (C) 2008 Elsevier B.V. All rights reserved.